A HUMAN HOMEOBOX GENE, HB24, INHIBITS DEVELOPMENT OF CD4+ T-CELLS AND IMPAIRS THYMIC INVOLUTION IN TRANSGENIC MICE

The HB24 gene encodes a diverged human homeodomain-containing protein known to be expressed in hematopoietic progenitors and activated lymphocytes. We have generated transgenic mice that express HB24 under the control of the T cell receptor beta chain promoter/enhancer. Analysis of T cells and thymocytes from the transgenic mice revealed a marked increase in activated cells as assessed by cell size profiles and interleukin-2 receptor expression. Within the thymus these changes were most pronounced in the CD4+CD8- subset. Strikingly, the normal development of CD4+ T cells in the transgenic mice was impaired. Single positive CD4 cells were reduced 35% in the thymus, and CD4+ T cells were reduced 90% in the spleen and lymph nodes compared to the controls. Similar findings were found both in young mice (6 weeks old) and in more elderly mice (1 y old). However, the thymuses of the elderly mice failed to undergo normal involution. Sera from HB24 transgenic mice had levels of IgG1 10-100-fold lower than sera from matched controls, most likely as a consequence of the decrease in CD4+ T cells. These transgenic mice provide a useful model for studying the role of HB24 in lymphocyte activation as well as for understanding the effects of abnormal T cell activation on thymic and T cell development.